1. Field of the Invention
The present invention relates to parvoviruses and to a cellular receptor for parvoviruses. Specifically, the invention relates to methods for detecting, preventing and treating infection of parvovirus, to methods of purifying and removing a parvovirus from samples, and to methods of gene therapy utilizing the parvovirus receptor.
2. Background Art
Parvoviruses are among the smallest DNA-containing viruses that infect animals and man. The parvoviridae family is divided into three genera: Parvovirus; Dependovirus (adeno-associated); and Densovirus. Parvoviruses range in size from 15 to 28 nm in diameter, lack a lipid membrane (non-enveloped), and contain a single strand of DNA. Parvoviruses are heat stable and generally resistant to chemical deactivating agents, which may account for their prevalence and persistence in the environment. In animals, many diseases such as canine parvovirus and feline panleukopenia exhibit high morbidity and high mortality in affected animal populations and the infections can persist endemically.
In man, the only known pathogenic member of this family is parvovirus B19. As with other parvoviruses, B19 is highly contagious and exhibits high morbidity in affected populations. Parvovirus B19 causes fifth disease in normal individuals (M. J. Anderson, et al. (1983)), transient aplastic crisis in patients with underlying hemolysis (N. S. Young; et al. (1988)), and chronic anemia due to persistent infection in immunocompromised patients (G. J. Kurtzman, et al. (1988) and N. Frickhofen et al. (1990)). Parvovirus infection in pregnancy can lead to hydrops fetalis and fetal loss (K. E. Brown (1989)) and/or congenital infection. B19 has also been implicated as the cause of chronic arthritis in adults where there is evidence of recent B19 infection, e.g., rheumatoid and inflammatory arthritis (B. J. Cohen et al. (1986) and D. G. White et al. There is currently no vaccine for protection from B19 infection.
B19 parvovirus exhibits extreme tropism for erythroid cells. Replication of B19 is restricted to human erythroid progenitor cells and the virus is dependent upon the presence of erythroprotein for replication in tissue culture systems (K. Ozawa et al. (1986) and K. Ozawa et al. (1987)). During B19 infection, the virus can be found in peripheral blood cells and the high levels of viremia seen with infection can lead to contamination of donor blood samples.
Despite the known pathogenicity of parvoviruses and the urgent need for methods to prevent, diagnose and treat parvovirus infections, a cell receptor has not been identified for any parvovirus. Early data suggested that the hemagglutinin of rodent parvoviruses might be a glycolipid (G. Cocuzza et al. (1969)), but similar studies suggest that feline panleukopenia virus binds to a glycoprotein on erythrocytes (M. Mochiziuki et al. (1978)). MVM (a rodent parvovirus) is thought to bind to a sialic acid containing glycoprotein, as pretreatment with neuraminidase or trypsin abolished binding (S. F. Cotmore et al. (1987)), and some evidence suggests that porcine parvovirus also binds to an undefined protein (M. J. Harding et al. (1992)). Even though there has been extensive study, the exact nature of the receptor is not known for any of the parvoviruses. Therefore a need exist to identify the cell receptors for parvoviruses and to provide a method for diagnosing, preventing and treating parvovirus infection utilizing the binding affinity for the receptor. Likewise, there exists a need to provide a method to purify and/or remove parvoviruses from samples. A cellular receptor for parvovirus also needs to be identified to assist researchers in searching for other species of parvoviruses and to aid in developing vaccines for parvoviruses.
The present invention satisfies that need by identifying a receptor for parvovirus B19 and by providing methods for diagnosis, treatment and prevention of B19 infection as well as methods for purification of B19 and methods of gene therapy utilizing the receptor for B19. Likewise, the methods utilized herein to identify the B19 receptor as well as the B19 receptor are applicable to other parvovirus receptors.